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- Christensen, DP, et al.
(författare)
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Lysine deacetylase inhibition prevents diabetes by chromatin-independent immunoregulation and β-cell protection
- 2014
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 111:3, s. 1055-1059
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes is due to immune-mediated pancreatic β-cell destruction. Lysine deacetylase inhibitors (KDACi) protect β-cells from inflammatory destruction in vitro and are promising immunomodulators. The orally active and clinically well-tolerated KDACi vorinostat and givinostat reverted diabetes in a mouse model of type 1 diabetes and counteracted inflammatory target cell damage. Importantly, these effects were achieved with doses that are safe and effective in human inflammatory diseases. Of note, the mechanism of action was compatible with transcription factor—rather than global chromatin—hyperacetylation, causing inhibition of transcription factor binding and reduction of proinflammatory gene expression in leukocytes and β-cells. These data provide a rationale for clinical trials of safety and efficacy of KDACi in patients with Type 1 diabetes.
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- Hansen, T. F., et al.
(författare)
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MicroRNA-126 and epidermal growth factor-like domain 7-an angiogenic couple of importance in metastatic colorectal cancer. Results from the Nordic ACT trial
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 109:5, s. 1243-1251
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study investigated the clinical importance of linked angiogenetic biomarkers to chemotherapy, combined with the anti-vascular endothelial growth factor A (anti-VEGF-A), as a first-line treatment in patients with metastatic colorectal cancer (mCRC). Methods: A total of 230 patients from a randomised phase III study were included. The primary microRNA-126 (pri-miRNA-126) A24G single-nucleotide polymorphism and the mature miRNA-126 were analysed by PCR using genomic DNA (full blood) and formalin-fixed paraffin-embedded tissue sections, respectively. The epidermal growth factor-like domain 7 (EGFL7) protein was visualised and quantified using immunohistochemistry. Results: High tumour expression of miRNA-126 was significantly related to a longer progression-free survival. The independent prognostic value of miRNA-126 was confirmed using a Cox regression analysis (hazard ratio = 0.49, 95% confidence interval = 0.29-0.84, P = 0.009). Although not significant, a relationship between EGFL7 expression and response rates is suggested, with EGFL7 expression at the invasive front being lower in responding patients than in the non-responders (P = 0.063). Conclusion: The results validate the previous findings on the prognostic value of miRNA-126 in mCRC and may suggest a relationship between treatment efficacy and EGFL7 expression. As miRNA-126 may target VEGF-A as well as EGFL7, the results may provide predictive information in relation to next-generation anti-angiogenetics.
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